PATHOLOGY

Differences in clinical outcome between primary Gleason grades
3 and 4: an analysis of 228 patients with a pathological Gleason score 7
Hattab EM, Koch MO, Eble JN, Zeng G, Daggy J, Cheng L
Department of Pathology, Indiana University School of Medicine, Indianapolis, IN
Mod Pathol. 2005; 18 (suppl. 1): abstract #665, 144A

• Background: In radical prostatectomy specimens, Gleason score 7 is among the most commonly assigned scores to prostate carcinoma accounting for 30-50% of the cases. Gleason score 7 is different from other more differentiated prostate carcinomas (tumors of Gleason scores 5 and 6), with a significantly worse outcome and higher rate of recurrence.
• Design: Five hundred and four patients underwent radical prostatectomy for prostate cancer. Two hundred and twenty-eight of the patients (45%) had a Gleason score of 7. Cases were analyzed for a variety of clinical and pathologic parameters.
• Results: Among 228 prostatic adenocarcinomas with Gleason score 7, 91(40%) had a primary Gleason grade of 4 and 137 (60%) had a primary grade of 3. Patients of the former group were more likely to have a higher pathological stage (P = 0.004), a higher rate of PSA recurrence (P = 0.008), and a higher incidence of vascular invasion (P = 0.039). In multiple logistic regression controlling for tumor stage (P = 0.046), surgical margin status (P = 0.0003), vascular invasion (P = 0.033), and preoperative PSA (P = 0.015), the primary Gleason grade was not an independent predictor of PSA recurrence (P = 0.141).
• Conclusions: Among patients with Gleason score 7, primary Gleason grade 4 carries the likelihood of higher tumor stage, higher rate of PSA recurrence and higher incidence of vascular invasion. It does not however independently predict a worse outcome after controlling for other known prognostic parameters that are associated with disease progression.
  
  
• Editorial Comment
  There are evidences showing that Gleason grade 4/5 may be superior to the Gleason score as a predictor of PSA progression following surgery (1,2). There are several ways to evaluate grade 4/5: primary Gleason grade 4 or 5, secondary Gleason grade 4 or 5, % of Gleason grade 4, % of Gleason 5 and combined % of Gleason grade 4 and 5 (3).
  Reporting of percentage Gleason grade 4/5 is cumbersome: there is the question of the reliability of the estimate (interobserver agreement) and how to quantitate percentage 4/5 cancer (4). It is our opinion that the easiest and straightforward way to evaluate the importance of grade 4/5 is to consider it either as the primary or secondary grade. In the present study of Hattab et al., grade 4 was considered either as the primary or the secondary grade in cases of Gleason score 7.
  In a recent quite similar study done in our Institution, we found that Gleason score > 7 or Gleason predominant grade 4/5 were more likely to have higher preoperative PSA, more extensive tumors, extraprostatic extension (pT3a) and seminal vesicle invasion (pT3b). However, only patients with Gleason predominant grade 4/5 had a statistical tendency for a shorter time to biochemical progression following radical prostatectomy (5).

References
1. Vis AN, Hoedemaker RF, van der Kwast TH, Schroder FH: Defining the window of opportunity in screening for prostate cancer: validation of a predictive tumor classification model. Prostate. 2001; 46: 154-162.
2. Noguchi M, Stamey TA, McNeal JE, Nolley R: Prognostic factors for multifocal prostate cancer in radical prostatectomy specimens: lack of significance of secondary cancers. J Urol. 2003; 170: 459-463.
3. Cheng L, Koch MO, Daggy J: The combined percentage of Gleason 4 and 5 is the best predictor of cancer progression after radical prostatectomy. Mod Pathol. 2004; 17(suppl. 1): 145A.
4. Humphrey PA: Gleason grading and prognostic factors in carcinoma of the prostate. Mod Pathol. 2004; 17: 292-306.
5. Guimarães MS, Billis A, Magna LA, Quintal MM, Ruabo T, Ferreira U: Gleason score vs Gleason predominant grade 4/5 as predictors of progression following radical prostatectomy. Mod Pathol. 2005; 18(suppl. 1): abstract #657.

Dr. Athanase Billis
Full-Professor of Pathology
State University of Campinas, Unicamp
Campinas, São Paulo, Brazil